Treatment of Skin by Spatial Modulation of Thermal Heating

ABSTRACT

Treating skin can include delivering a beam of radiation to a target region of the skin to cause a zone of thermal injury including a lateral pattern of varying depths of thermal injury distributed along the target region. The lateral pattern includes at least one first sub-zone of a first depth of thermal injury laterally adjacent to at least one second sub-zone of a second depth of thermal injury. The first depth is greater than the second depth. The at least one first sub-zone of the first depth and the at least one second sub-zone of the second depth extend from a surface of the target region of the skin to form a substantially continuous surface thermal injury. The at least one first sub-zone of the first depth and the at least one second sub-zone of the second depth are substantially heated to at least a critical temperature.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of and priority to U.S. ProvisionalApplication Ser. No. 60/813,729 filed Jun. 14, 2006, which is owned bythe assignee of the instant application and the disclosure of which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates generally to a skin treatment using radiation. Inparticular, the invention relates to a method for treating skin using abeam of radiation to cause spatially modulated thermal injury of theskin sufficient to elicit a healing response and improvement in theskin.

BACKGROUND OF THE INVENTION

Ablative resurfacing of skin with lasers can be an effective treatmentfor skin conditions such as wrinkles. However, ablative resurfacing canhave undesirable post-treatment side effects. For example, crusting,oozing, erythema can last up to 5 weeks. Furthermore, permanent scarringis a possible long-term side effect of ablative resurfacing. Such sideeffects can be a deterrent to individuals who otherwise desiretreatment.

Improved treatments with reduced side effects include formingsub-surface thermal damage of skin, while leaving the top layer intactby combining heating and surface cooling. However, the results ofsub-surface methods can be less dramatic than those achieved by ablativeresurfacing. Other improvements include fractional resurfacingtechniques, that treat skin in discrete spots and leave the skin betweenthe spots untreated.

Fractional resurfacing technologies can have advantages including lowerincidences of side-effects and expedited healing. These advantages canresult from the undamaged regions providing blood and nutrients to theadjacent damaged regions and accelerating the healing process. Ablativeresurfacing and technologies that include inducing uniform damagecorresponding to coverage of an entire region can include higherefficacy at the cost of increased side effects.

SUMMARY OF THE INVENTION

The invention, in various embodiments, combines many of the advantagesof ablative resurfacing with those of fractional methods. Skin can betreated by delivering a beam of radiation to a target region to cause azone of thermal injury. The zone can include a lateral pattern ofvarying depths of thermal injury distributed along the target region.The lateral pattern can include at least one first sub-zone of a firstdepth of thermal injury laterally adjacent to at least one secondsub-zone of a second depth of thermal injury. The at least one firstsub-zone of the first depth and the at least one second sub-zone of thesecond depth can extend from a surface of the target region of the skinto form a substantially continuous surface thermal injury.

A beam of radiation can have a modulated spatial profile such that thefluence, the intensity, and/or the wavelength delivered to the skin canbe varied. The spatial profile determines the depth of thermal injury tothe skin. A beam of radiation can be delivered to a region of skin tocause modulated spatial profile of temperature, such that the depth ofdamage to the skin is varied. An advantage of the invention is that alarge target region can be formed with damaged regions adjacent tosubstantially undamaged regions within the target region, together witha substantially continuous surface thermal injury. The substantiallyundamaged regions can be undamaged or less damaged than the damagedregions. Other advantages include: improved treatment efficacyinitiating from zones corresponding to deeper first damage zones, highcoverage of a treatment region corresponding to deeper first damagezones and less deep second damage zones, improved efficacy relating toforming a substantially continuous surface thermal injury, and improvedpost-treatment healing initiating from zones corresponding to less deepsecond damage zones.

In one embodiment, the treatment can be used to treat wrinkles or forskin rejuvenation. However, the treatment is not limited to treatingwrinkles or skin rejuvenation. A beam of radiation can be deliverednon-invasively to affect the skin.

In one aspect, the invention features a method for treating skinincluding delivering a beam of radiation to a target region of the skin,to cause a zone of thermal injury including a lateral pattern of varyingdepths of thermal injury distributed along the target region. Thelateral pattern includes at least one first sub-zone of a first depth ofthermal injury laterally adjacent to at least one second sub-zone of asecond depth of thermal injury. The first depth is greater than thesecond depth. The at least one first sub-zone of the first depth and theat least one second sub-zone of the second depth extend from a surfaceof the target region of the skin to form a substantially continuoussurface thermal injury. Both the at least one first sub-zone of thefirst depth and the at least one second sub-zone of the second depth aresubstantially heated to at least a critical temperature to cause thethermal injury.

In another aspect, the invention features a method for treating skinincluding delivering a beam of radiation to a first portion of a targetregion of the skin, to heat the first portion to at least a criticaltemperature to cause a first thermal injury. The method also includestranslating the beam of radiation to a second portion of the targetregion. Additionally, the method includes delivering the beam ofradiation to the second portion of the target region, to heat the secondportion to at least the critical temperature to cause a second thermalinjury. The first thermal injury and the second thermal injury extendfrom a surface of the target region of the skin to form a substantiallycontinuous surface thermal injury and form a lateral pattern of varyingdepths of thermal injury distributed along the target region.

In yet another aspect, the invention features an apparatus for treatingskin including a source of a beam of radiation and a modulator. Themodulator receives the beam of radiation and forms a modulated spatialprofile of the beam including a first plurality of first regions at afirst fluence and a second plurality of second regions at a secondfluence. The first fluence is greater than the second fluence, and eachfirst region is spaced from an adjacent first region by a respectivesecond region. The apparatus also includes a device for delivering thebeam of radiation to a target region of skin to cause a zone of thermalinjury including a lateral pattern of varying depths of thermal injurydistributed along the target region. The lateral pattern includes atleast one first sub-zone of a first depth of thermal injury laterallyadjacent to at least one second sub-zone of a second depth of thermalinjury. The first depth is greater than the second depth. The at leastone first sub-zone of the first depth and the at least one secondsub-zone of the second depth extend from a surface of the target regionof the skin to form a substantially continuous surface thermal injury.The at least one first sub-zone of the first depth and the at least onesecond sub-zone of the second depth are substantially heated to at leasta critical temperature to cause the thermal injury.

In other examples, any of the aspects above, or any apparatus or methoddescribed herein, can include one or more of the following features.

In various embodiments, the lateral pattern has a substantiallysinusoidal cross sectional injury profile. The method can includedelivering the beam of radiation to the target region to form aone-dimensional lateral pattern of varying depths of thermal injury. Themethod can include delivering the beam of radiation to the target regionto form a two-dimensional lateral pattern of varying depths of thermalinjury. The first depth and the second depth can be between about 2 mmand about 0.02 mm. The first depth can be about 1.5 mm and the seconddepth can be about 0.05 mm.

In some embodiments, the critical temperature is below about 100° C.,95° C., 90° C., 85° C., 80° C., 75° C., 70° C., 65° C., 60° C., 55° C.,or 50° C. The thermal injury can include at least one of ablation,coagulation, necrosis, and acute thermal injury of skin. The method caninclude heating the at least one first sub-zone and the at least onesecond sub-zone to substantially the same temperature.

In certain embodiments, the method includes cooling the surface of theskin, to control the surface thermal injury. The method can includecooling the surface of the skin, to prevent unwanted surface thermalinjury. The method can include cooling the target region of skin toproduce at least one first region at a first temperature and at leastone second region at a second temperature, the first temperature beinggreater than the second temperature, the at least one first regioncorresponding to the at least one first sub-zone, and the at least onesecond region corresponding to the at least one second sub-zone. Themethod can include cooling the target region of skin to produce at leastone first region cooled to a first depth and at least one second regioncooled to a second depth, the first depth being less than the seconddepth, the at least one first region corresponding to the at least onefirst sub-zone, and the at least one second region corresponding to theat least one second sub-zone.

In various embodiments, the method includes delivering a beam ofradiation having a first wavelength to the at least one first sub-zoneto cause the first depth of thermal injury and a beam of radiationhaving a second wavelength to the at least one second sub-zone to causethe second depth of thermal injury. The method can include delivering abeam of radiation having a first fluence to the at least one firstsub-zone to cause the first depth of thermal injury and a beam ofradiation having a second fluence to the at least one second sub-zone tocause the second depth of thermal injury. The method can includedelivering a beam of radiation having a first pulse duration to the atleast one first sub-zone to cause the first depth of thermal injury anda beam of radiation having a pulse duration to the at least one secondsub-zone to cause the second depth of thermal injury.

In some embodiments, the at least two first sub zones of the first depthare separated by a center to center distance of about 0.05 mm to about20 mm. The at least one first sub-zone of the first depth can have anaspect ratio of diameter:depth up to about 0.1:10. The at least onesecond sub-zone of the second depth can have an aspect ratio ofdiameter:depth up to about 0.1:10.

In certain embodiments, the apparatus includes a cooling system forcontrollably cooling at least a portion of the target region of skin, tocontrol the thermal injury within the target region. The apparatus caninclude a cooling system for cooling the target region of skin toproduce at least one first region at a first temperature and at leastone second region at a second temperature, the first temperature beinggreater than the second temperature, the at least one first regioncorresponding to the at least one first sub-zone, and the at least onesecond region corresponding to the at least one second sub-zone. In oneembodiment, the apparatus includes a cooling system for cooling thetarget region of skin to produce at least one first region cooled to afirst depth and at least one second region cooled to a second depth, thefirst depth being less than the second depth, the at least one firstregion corresponding to the at least one first sub-zone, and the atleast one second region corresponding to the at least one secondsub-zone.

Other aspects and advantages of the invention can become apparent fromthe following drawings and description, all of which illustrate theprinciples of the invention, by way of example only.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the invention described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the invention.

FIG. 1 shows an exemplary cross-section of skin.

FIG. 2 shows an exemplary embodiment of a system for treating skin.

FIGS. 3A-3B show views of an exemplary cross-section of a region ofskin.

FIGS. 4A-4B show a relationship that can be used to control thetemperature and thermal injury at a depth of a region of skin.

FIGS. 5A-5B shows examples of spatial modulation of a beam of radiation.

FIG. 6 shows an exemplary embodiment of a device for treating a regionof skin.

FIGS. 7A-7C show exemplary treatments of skin using cooling.

FIGS. 8A-8B show exemplary embodiments of a surface of a treated regionof skin with a pattern of varying depths of thermal injury.

FIG. 9 shows a ray trace of modulated electromagnetic radiation.

FIG. 10 shows a contour plot of energy density on skin created bymodulated electromagnetic radiation.

FIG. 11 shows a plot of intensity variation across skin created bymodulated electromagnetic radiation.

DESCRIPTION OF THE INVENTION

FIG. 1 shows an exemplary cross-section of skin 1 including a region ofepidermis 2, a region of dermis 3, a region of subcutaneous tissue 4,and a surface of the skin 5. In one embodiment, the skin 1 can be aregion of human skin with wrinkles. A beam of radiation 6 can bedelivered to the skin 1 to treat at least a region of skin, including aregion of epidermis 2 and/or a region of dermis 3. Skin treatments caninclude skin rejuvenation and treatments for wrinkles, vessels,pigmentation, scarring, and acne.

A therapeutic injury can be induced with electromagnetic radiation inthe visible to infrared spectral region. A wavelength of light thatpenetrates into at least a portion of skin can be used. Chromophores caninclude blood (e.g., oxyhemoglobin and deoxyhemoglobin), collagen,melanin, fatty tissue, and water. Light sources can include lasers,light emitting diodes, or an incoherent source, and can be either pulsedor continuous. In one embodiment, a light source can be coupled to aflexible optical fiber or light guide, which can be introducedproximally to a target region skin. The light source can operate at awavelength with depth of penetration into skin that is less than thethickness of the target region of skin.

In various embodiments, skin in a target region is heated to a criticaltemperature to cause thermal injury. In certain embodiments, thecritical temperature is below about 100° C. In other embodiments, thecritical temperature is below about 95° C., 90° C., 85° C., 80° C., 75°C., 70° C., 65° C., 60° C., 55° C., or 50° C. In one embodiment, thecritical temperature is the temperature associated with ablation,coagulation, necrosis, and/or acute thermal injury of skin.

FIG. 2 shows an exemplary embodiment of a system 10 for treating skin.The system 10 can be used to non-invasively deliver a beam of radiationto a target region of skin. The system 10 includes an energy source 12and a delivery system 13. In one embodiment, a beam of radiationprovided by the energy source 12 is directed via the delivery system 13to a target area. In the illustrated embodiment, the delivery system 13includes a fiber 14 having a circular cross-section and a handpiece 16.A beam of radiation can be delivered by the fiber 14 to the handpiece16, which can include an optical system (e.g., an optic or system ofoptics) to direct the beam of radiation to the target area. A user canhold or manipulate the handpiece 16 to irradiate the target area. Thehandpiece 16 can be positioned in contact with a skin surface, can bepositioned adjacent a skin surface, can be positioned proximate a skinsurface, can be positioned spaced from a skin surface, or a combinationof the aforementioned. In the embodiment shown, the handpiece 16includes a spacer 18 to space the delivery system 13 from the skinsurface. In one embodiment, the spacer 18 can be a distance gauge, whichcan aid a practitioner with placement of the handpiece 16.

In various embodiments, the energy source 12 can be an incoherent lightsource, a coherent light source (e.g., a laser), a solid state laser, adiode laser, a fiber coupled diode laser array, an optically combineddiode laser array, and/or a high power semiconductor laser. In someembodiments, two or more sources can be used together to effect atreatment. For example, an incoherent source can be used to provide afirst beam of radiation while a coherent source provides a second beamof radiation. The first and second beams of radiation can share a commonwavelength or can have different wavelengths. In an embodiment using anincoherent light source or a coherent light source, the beam ofradiation can be a pulsed beam, a scanned beam, or a gated continuouswave (CW) beam.

In various embodiments, the source of electromagnetic radiation caninclude a fluorescent pulsed light (FPL) or an intense pulsed light(IPL) system. For example, the system can be a LIGHTSTATION™ (by CandelaCorporation of Wayland, Mass.), or an OMNILIGHT™, NOVALIGHT™, orPLASMALITE™ system (by American Medical Bio Care of Newport Beach,Calif.). However, the source of electromagnetic radiation can alsoinclude a laser, a diode, a coherent light source, an incoherent lightsource, or any other source of electromagnetic radiation. FPLtechnologies can utilize laser-dye impregnated polymer filters toconvert unwanted energy from a xenon flashlamp into wavelengths thatenhance the effectiveness of the intended applications. FPL technologiescan be more energy efficient and can generate significantly less heatthan comparative IPL systems. A FPL system can be adapted to operate asa multi-purpose treatment system by changing filters or handpieces toperform different procedures. For example, separate handpieces allow apractioner to perform tattoo removal and other vascular treatments. Anexemplary FPL system is described in U.S. Pat. No. 5,320,618, thedisclosure of which is herein incorporated by reference in its entirety.

In various embodiments, the beam of radiation can have a wavelengthbetween about 380 nm and about 2600 nm. In certain embodiments, the beamof radiation can have a wavelength between about 1,200 nm and about2,600 nm, between about 1,200 nm and about 1,800 nm, or between about1,300 nm and about 1,600 nm. In one embodiment, the beam of radiationhas a wavelength of about 1,500 nm. In other embodiments, the beam ofradiation has a wavelength up to about 2,100 nm or up to about 2,200 nm.

In various embodiments, the beam of radiation can have a fluence ofabout 1 J/cm² to about 500 J/cm². For a given wavelength of radiation, arange of effective fluences can be approximated. Because radiation ofwavelength between about 380 nm and about 2600 nm is absorbed by water,and because skin is about 70% water, the absorption coefficient of skincan be approximated as 70% of the absorption coefficient of water.Because the absorption coefficient of water is a function of thewavelength of radiation, the desired fluence depends on the chosenwavelength of radiation. The fluence necessary to produce a desireddamage depth can be approximated as the fluence that will raise thetemperature to the critical temperature at the desired penetrationdepth, calculated as:[3*μ_(a)*(μ_(a)+μ_(s)(1−g))]^(−0.5)

where μ_(a), μ_(s), and g are absorption coefficient, scatteringcoefficient, and the anisotropy factor of skin, respectively. TABLE 1Approximate fluence range to produce a first sub-zone of damage using agiven wavelength. Wavelength (nm) Fluence (J/cm²) 1180 100-498 1200100-498 1220 109-545 1240 118-588 1260 116-582 1280 106-528 1300  93-4661320  75-375 1340  65-326 1360  56-280 1380  29-146 1400 19-96 142014-70 1440 11-54 1460 11-55 1480 15-73 1500 18-88 1520  22-111 1540 20-101 1560  23-115 1580  26-130 1600  26-132 1620  31-153 1640  36-1781660  39-196 1680  40-198 1700  40-200 1720  35-174 1740  29-145 1760 25-124 1780  26-128 1800  26-129 1820  23-115 1840  23-117 1860  22-1091880 10-50 1900  5-23 1920  3-14 1940  3-13 1960  3-15 1980  3-17 2000 4-22 2020  6-28 2040  7-35 2060  8-40 2080 10-49 2100 12-58 2120 13-652140 15-76 2160 17-83 2180 18-90 2200 19-94 2220 19-96 2240 19-94 226018-90 2280 16-78 2300 14-69 2320 12-58 2340 10-49 2360  8-42 2380  7-362400  6-31 2420  5-26 2440  5-23 2460  4-20 2480  4-18 2500  3-17 2520 3-15 2540  3-14 2560  3-13 2580  2-12 2600  2-10

In various embodiments, the fluence used to produce a second sub-zone ofdamage is less than the fluence used to produce a first sub-zone ofdamage. In certain embodiments, the fluence used to produce a secondsub-zone of damage is about 10% of the fluence used to produce a firstsub-zone of damage.

In various embodiments, a desired penetration depth of light into theskin (and a corresponding depth of thermal injury) can be targeted byselecting a wavelength of a beam of radiation. For example, a waterabsorption coefficient can be taken from G. M. Hale and M. R. Querry,“Optical constants of water in the 200 nm to 200 μm wavelength region,”Appl. Opt., 12, 555-563, (1973) and an Optical Penetration Depth (OPD)can be calculated using a diffusion approximation. As described above,μ_(a) of skin is taken as μ_(a) of water multiplied by 0.7. The productof scattering coefficient and (1-anisotropy factor) is taken as 12 cm⁻¹.TABLE 2 Approximate wavelength for a corresponding desired penetrationdepth. lambda (nm) OPD (microns) OPD (mm) 1180 1896.68 1.90 1200 1896.681.90 1220 1989.42 1.99 1240 2071.04 2.07 1260 2058.80 2.06 1280 1957.111.96 1300 1832.38 1.83 1320 1631.35 1.63 1340 1399.75 1.40 1360 1110.541.11 1380 692.68 0.69 1400 431.17 0.43 1420 279.87 0.28 1440 226.74 0.231460 229.34 0.23 1480 288.97 0.29 1500 333.69 0.33 1520 393.98 0.39 1540445.51 0.45 1560 512.22 0.51 1580 583.96 0.58 1600 651.32 0.65 1620713.46 0.71 1640 785.79 0.79 1660 831.29 0.83 1680 836.88 0.84 1700842.55 0.84 1720 773.46 0.77 1740 689.83 0.69 1760 626.39 0.63 1780575.87 0.58 1800 580.12 0.58 1820 538.51 0.54 1840 492.55 0.49 1860391.16 0.39 1880 213.05 0.21 1900 111.13 0.11 1920 67.16 0.07 1940 64.380.06 1960 72.32 0.07 1980 82.28 0.08 2000 106.81 0.11 2020 128.89 0.132040 156.06 0.16 2060 176.11 0.18 2080 211.15 0.21 2100 239.41 0.24 2120262.39 0.26 2140 296.35 0.30 2160 319.62 0.32 2180 338.03 0.34 2200349.91 0.35 2220 356.02 0.36 2240 349.28 0.35 2260 338.77 0.34 2280304.49 0.30 2300 277.13 0.28 2320 240.27 0.24 2340 208.26 0.21 2360183.15 0.18 2380 161.22 0.16 2400 142.20 0.14 2420 121.74 0.12 2440109.92 0.11 2460 97.31 0.10 2480 87.44 0.09 2500 83.58 0.08 2520 74.660.07 2540 70.44 0.07 2560 66.71 0.07 2580 58.99 0.06 2600 51.05 0.05

FIG. 3A shows an exemplary cross-section 20 of a region of skinincluding a region of skin surface 22, a region of epidermis 24, aregion of dermis 26, and a zone of thermal injury 28 including a patternof varying depths of thermal injury. The pattern includes at least onefirst sub-zone 30 of a first depth of thermal injury adjacent to atleast one second sub-zone 32 of a second depth of thermal injury. Thefirst depth is greater than the second depth. In various embodiments,the depth 34 of thermal injury in the first sub-zone can be measuredfrom the skin surface 22. In various embodiments, the depth 36 ofthermal injury in the second sub-zone can be measured from the skinsurface 22. In various embodiments, the diameter 38 of thermal injury ina sub-zone can be measured on the skin surface 22.

The at least one first sub-zone 30 of the first depth of thermal injuryand the at least one second sub-zone 32 of the second depth of thermalinjury extend from the surface 22 of the target region to form asubstantially continuous surface thermal injury. The at least one firstsub-zone 30 of the first depth and the at least one second sub-zone 32of the second depth are substantially heated to at least a criticaltemperature to cause the thermal injury. In one embodiment, thetemperature within the at least one first sub-zone 30 of the first depthand the at least one second sub-zone 32 can vary at or above thecritical temperature and, accordingly, the degree of thermal injury canalso vary at or above a pre-determined amount. In another embodiment,the temperature within the at least one first sub-zone 30 of the firstdepth and the at least one second sub-zone 32 can be substantially thesame and, accordingly, the degree of thermal injury can also besubstantially the same.

FIG. 3B shows a three-dimensional view of the cross-section 20 of theregion of skin in FIG. 3A, including the region of skin surface 22 and athree-dimensional zone of thermal injury 28 including a pattern ofvarying depths of thermal injury. The exemplary pattern of varyingdepths of thermal injury is distributed contiguously along the surface22 of the target region and includes a three-dimensional zone of thermalinjury 28 having a pattern with the three-dimensional first sub-zone 30of a first depth of thermal injury contiguous along the skin surfacewith the three-dimensional second sub-zone 32 of a second depth ofthermal injury. In various embodiments, the depth 34 of thermal injuryin the first sub-zone can be measured from the skin surface 22. Invarious embodiments, the depth 36 of thermal injury in the secondsub-zone can be measured from the skin surface 22. In variousembodiments, the diameter 38 of thermal injury in a sub-zone can bemeasured on the skin surface 22.

A first sub-zone of a first depth of thermal injury can improve theefficacy of treatment by including an acute thermal injury. Asubstantially continuous surface thermal injury can improve the efficacyof treatment by including surface ablation and/or inducing a surfacepeel. A second sub-zone of a second depth of thermal injury can improvepost-treatment healing of skin. A second sub-zone of a second depth ofthermal injury can improve post-treatment healing of an adjacent firstsub-zone of a first depth of thermal injury. In various embodiments,treatment efficacy can be improved by forming first sub-zones of thermalinjury adjacent to second sub-zones of thermal injury. In someembodiments, treatment efficacy can be improved by forming firstsub-zones of thermal injury underlying a substantially continuoussurface thermal injury. In certain embodiments, post-procedure healingcan be improved by improved flow of blood and nutrients provided by asecond sub-zone.

In various embodiments, a sub-zone of thermal damage can include athree-dimensional region of epidermis and/or a region of dermis. Forexample, in certain embodiments, a first sub-zone can includethree-dimensional regions of epidermis and dermis, while a secondsub-zone can include three-dimensional regions of epidermis.

In various embodiments, the pattern of thermal injury can be acontinuously varying pattern (e.g., a sinusoidal-like or wave-likepattern when viewed in two-dimensions or an “egg carton” like patternwhen viewed in three-dimensions). In some embodiments, the pattern ofthermal injury can be a continuous surface injury with periodic orirregular regions of deeper thermal injury (e.g., a step-function likepattern when viewed in two dimensions). However, the pattern of thermalinjury is not limited to any specific design. Contiguous regions in skinof subsurface injury without surface injury can be overlaid by discreteregions of added surface injury. In certain embodiments, contiguousregions of superficial injury can be overlaid by discrete regions ofsuperficial tissue ablation.

In some embodiments, a three-dimensional pattern of varying depthsand/or varying severity of thermal injury within skin can be formed.Regions of more deeply and/or severely injured skin can be contiguouswith regions of less deeply and/or severely damaged skin. In certainembodiments, first regions of skin with sub-surface injury and withoutsurface injury are formed. Such first regions can be contiguous withsecond regions of skin without sub-surface injury and with surfaceinjury. In various embodiments, wounds in the skin that require longrecovery periods are avoided. For example, effective treatment of skincan be provided without forming large or contiguous areas of acuteinjury or necrosis.

As a beam or radiation penetrates skin, the fluence (J/cm²) decreases inan approximately exponential fashion. The rate of decrease in fluence isdependent upon the absorption and scattering properties of skin. A localtemperature increase due to absorbed radiation within the skin is aproduct of the local absorption coefficient and a local fluence dividedby the volumetric specific heat. Since absorption and volumetricspecific heat can be considered approximately constant within a regionof skin, the local temperature rise can be considered proportional tothe fluence.

Thermal damage to skin forms at temperatures at, or exceeding, acritical temperature (T_(c)). Little or no thermal damage to skin formsat temperatures below T_(c). Therefore, depth of thermal damage to skinis approximately equal to the depth of skin that is exposed to atemperature of, or exceeding, T_(c).

FIG. 4A shows a relationship that can be used to control the temperatureat a depth of a region of skin. For a given temperature (T), a greaterfluence can be selected if heating to a greater depth is desired and alesser fluence can be selected if heating to a lesser depth is desired.This relationship can provide a method to control the depth to which aspecific temperature is achieved.

FIG. 4B shows a relationship that can be used to control a depth ofthermal injury to a region of skin. A lower fluence produces a smallerdepth of thermal injury and a higher fluence produces a greater depth ofthermal injury. For a given degree of damage, a greater fluence can beselected if a greater depth is desired and a lesser fluence can beselected if a lesser depth is desired. Therefore, by modulating thefluence, one can modulate the depth and temperature within a region ofskin.

To form deeper sub-zones of thermal injury, more penetrating wavelengthsof radiation can be used. More penetrating wavelengths can be combinedwith longer pulse durations to increase thermal damage. In certainembodiments, more penetrating wavelengths can be combined with surfacecooling to spare overlying tissue.

To form shallower sub-zones of thermal injury, less penetratingwavelengths can be used. Less penetrating wavelengths can be combinedwith shorter pulse durations. Less penetrating wavelengths can be usedwithout surface cooling or with moderate cooling. Less penetratingwavelengths can also be used with surface cooling to maintain atemperature about a T_(c) (e.g., allow formation of thermal injury, butprevent necrosis or acute thermal injury).

In various embodiments a beam of radiation with spatially varyingintensity; a beam of radiation with spatially varying exposure time orpulse duration; a beam of radiation with spatially varying wavelengthswherein certain regions of the beam include a more penetratingwavelength and other parts include a less penetrating wavelength; and/ora beam of radiation with spatially varying wavelengths with preferentialabsorption in different skin structures (e.g., a beam includingwavelengths with strong water absorption interspersed with wavelengthswith strong blood absorption) can be delivered to a target region of theskin to cause a zone of thermal injury including a lateral pattern ofvarying depths.

In various embodiments, a pulse duration can be between about 1 ms andabout 1 min. Shorter pulse durations can be between about 1 ms and about100 ms. Longer pulse durations can be between about 100 ms and about 1min.

In various embodiments, a depth of thermal injury in a deeper sub-zonecan be up to about 2 mm. In certain embodiments, a depth of thermalinjury in a shallower sub-zone can be up to about 50 μm. In oneembodiment, deeper sub-zones having a depth of about 400-800 μm areadjacent to shallower sub-zones having a depth of about 50 μm. Inanother embodiment, deeper sub-zones having a depth of about 400-800 μmare adjacent to shallower sub-zones having a depth of about 25 μm. Instill another embodiment, deeper sub-zones having a depth of about 1.5mm are adjacent to shallower sub-zones having a depth of about 50 μm

In various embodiments, adjacent sub-zones of thermal damage distributedcontiguously along the surface of the target region can correspond toabout 100% coverage of the surface of the target region (e.g., asubstantially continuous surface injury). In certain embodiments,adjacent sub-zones of thermal damage distributed contiguously along thesurface of the target region can correspond to less than 100% coverageof the surface of the target region.

In various embodiments, the target region includes about 0.5% to about99% sub-zones of greater depth. In one embodiment, the target regionincludes about 5% to about 50% sub-zones of greater depth. In oneembodiment, the target region includes about 15% to about 30% sub-zonesof greater depth.

In various embodiments, a diameter of a deeper sub-zone of thermaldamage can be between about 20 μm and about 2 mm. In some embodiments, adiameter of a shallower sub-zone of thermal damage can be between about100 μm and about 1000 μm. In various embodiments, spacing between deepersub-zones can be between about 2 to about 5 times the diameter of thedeeper sub-zone. In various embodiments, spacing between shallowersub-zones is the sum of the diameters of the deeper and the shallowersub-zones. In certain embodiments, a sub-zone of thermal damage can havean aspect ratio of diameter:depth greater than 1:2. In one embodiment, asub-zone of thermal damage has an aspect ratio greater than 1:4. Inanother embodiment, a sub-zone of thermal damage can have an aspectratio up to about 0.1:10.

FIG. 5A shows an example of spatial modulation of a beam of radiation. Asingle 40 beam of radiation is incident on a modulator 41, which forms aspatially modulated 42 beam of radiation 42. In various embodiments, themodulator 41 can be an optical device and/or an electromagnetic device.For example, the modulator 41 can be a lens, a micro lens array, asystem of lenses, a diffractive optic in combination with a lens, oranother optical device capable of varying the fluence of the beam ofradiation 40. In certain embodiments, the modulator is an acousto-opticmodulator. In certain embodiments, the single 40 beam can be modulatedto form a plurality of discrete beams.

FIG. 5B shows another example of spatial modulation of a beam ofradiation. A plurality 44 of beams of radiation are incident on amodulator 41, which forms the spatially modulated 42 beam of radiation.Regions of the discrete beams can overlap to form the spatiallymodulated beam of radiation 42.

In various embodiments, an optical fiber can be scanned over a surfaceof skin to deliver a spatially modulated beam of radiation to a targetregion of skin. In various embodiments, an optical fiber bundle can beused to deliver a plurality of beams of radiation. In certainembodiments, the optical fiber bundle can operate in a scanning modeover a surface of skin. In certain embodiments, the optical fiber bundlecan operate in a stamping mode over a surface of skin. The diameter of aregion of a surface of skin treated in each stamp can range from about 1mm to about 50 mm. An optical fiber can be a fiber laser.

FIG. 6 shows an exemplary embodiment of a device for treating a regionof skin. A cross-section of skin 50 includes a skin surface 51 and aregion 52 of thermal injury underlying the surface 51. A source 53 of abeam of radiation is coupled to a modulator 54. The source 53 can scan55 along to the skin surface 51, to deliver a beam of radiation 56 to atarget region of skin. The modulator 54 can modulate the fluence, theintensity, or the wavelength of the beam 56 and/or the rate oftranslation of the source 53.

By varying the fluence, the intensity, or the wavelength of the beam 56,the depth of injury can be controlled. Increasing the intensity of thebeam 56 delivered to skin 50 can form a deeper zone of injury, e.g., afirst sub-zone 57. Decreasing the intensity of the beam 56 delivered toskin 50 can form a shallow zone of injury, e.g., a second sub-zone 58.Varying the fluence or the intensity of the beam 56 can form a modulatedspatial pattern 59 of thermal injury in skin.

By varying the rate of translation along the skin, the depth of thermalinjury can be controlled. Decreasing the rate over skin 50 can increasethe total fluence delivered to a particular region, forming a deeperzone of injury, e.g., a first sub-zone 57. Increasing the rate over skin50 can decrease the total fluence delivered to a particular region,forming a shallow zone of injury, e.g., a second sub-zone 57. Varyingthe rate of translation along the skin, can form a modulated spatialpattern 59 of thermal injury in skin.

In some embodiments, methods can include sequentially applying differentcombinations of radiation wavelength, intensity, or cooling such that apattern of thermal injury achieved in a given pass is different thanthat achieved in a subsequent pass.

A cooling system can be used to modulate the temperature in a region ofskin and/or minimize unwanted thermal injury to untargeted skin. Forexample, the delivery system 13 shown in FIG. 2 can be used to cool theskin before, during, or after delivery of radiation, or a combination ofthe aforementioned. Cooling can include contact conduction cooling,evaporative spray cooling, convective air flow cooling, or a combinationof the aforementioned. Cooling can include applying a template to theskin and employing contact, evaporative, or convective cooling to coolat least an exposed portion of the skin. In one embodiment, thehandpiece 16 includes a skin contacting portion that can be brought intocontact with a region of skin. The skin contacting portion can include asapphire or glass window and a fluid passage containing a cooling fluid.The cooling fluid can be a fluorocarbon type cooling fluid, which can betransparent to the radiation used. The cooling fluid can circulatethrough the fluid passage and past the window to cool the skin.

A spray cooling device can use cryogen, water, or air as a coolant. Inone embodiment, a dynamic cooling device (e.g., a DCD available fromCandela Corporation) can be used to cool the skin. For example, thedelivery system 13 shown in FIG. 2 can include tubing for delivering acooling fluid to the handpiece 16. The tubing can be connected to acontainer of a low boiling point fluid, and the handpiece can include avalve for delivering a spurt of the fluid to the skin. Heat can beextracted from the skin by virtue of evaporative cooling of the lowboiling point fluid. In one embodiment, the fluid is a non-toxicsubstance with high vapor pressure at normal body temperature, such as aFreon or tetrafluoroethane.

By cooling only a portion of the target region or by cooling differentportions of the target region to different extents, the degree ofthermal injury of individual portions of the target region can becontrolled. By cooling with spatially varying duration and/or by coolingwith spatially varying temperature, the degree of thermal injury ofindividual portions of the target region can also be controlled.

FIG. 7A shows an exemplary treatment of skin using cooling. Across-section of a region of skin 60 includes a skin surface 61. Acooling plate 62 is applied to the skin surface 61, and a region 63 ofskin not in contact with the cooling plate 62 is formed. A beam ofradiation 64 is delivered to the region of skin 60, to treat the skin.

The cooling plate 62 can be applied to the skin surface 61 prior to orduring delivery of the beam of radiation 64. In some embodiments, thecooling plate 62 can have at least one open region, corresponding to theregion 63 of skin not in contact with the cooling plate 62.

The cooling plate 62 can cool different regions of the target region todifferent extents thus modulating a spatial profile of temperature inthe skin 60. For example, skin underlying the region 63 not in contactwith the cooling plate 62 can be cooled to a first temperature, and skinunderlying the cooling plate 62 can be cooled to a second temperature.The first temperature is greater than the second temperature.

In some embodiments, the cooling plate 62 can be continuous (e.g., nothave open regions), but have regions of varying thickness. Thickerregions of the cooling plate can extract more heat from the skin thanthinner regions, thus a deeper zone of thermal injury can be formedunder the thinner regions.

In FIG. 7A skin region 66 represents a deeper zone of thermal injury.Skin region 68 represents a shallower zone of thermal injury, e.g.,where the skin 60 is substantially undamaged.

FIG. 7B shows another exemplary treatment of skin using cooling. Across-section of a treatment region of skin 70 is treated with a cryogenspray 71 and a beam 72 of radiation. At least a region of the skinsurface 73 is in contact with a laser-transparent spray screen 74, whichcan be applied to the skin surface 73 prior to delivery of the cryogenspray 71. The cryogen spray 71 can be applied prior to or duringdelivery of the beam 72 of radiation to cool different regions of thetarget region to different extents.

The screen 74 can modulate a spatial profile of temperature in skin bypreventing the cryogen spray 71 from reaching at least a region of thesurface 73. In certain embodiments, the screen 74 is not used and thecryogen spray 71 is applied to the skin surface 73 in pools of varyingdepth. A deeper pool can extract more heat from the skin surface 73,thus forming a region of shallow injury when radiation is delivered.

In FIG. 7B the beam 72 of radiation is delivered to the surface 73 ofskin with at least one underlying region 76 of skin of first temperatureand at least one underlying region 77 of skin of second temperature. Thefirst temperature is greater than the second temperature. Delivery ofthe beam 72 of radiation can increase the temperature in the targetregion. In a region 76 of skin of first temperature, delivery of thebeam 72 of radiation can increase the temperature above a criticaltemperature, forming a first sub-zone 75 of thermal injury. In a region77 of skin of second temperature, delivery of the beam of radiation canincrease the temperature to a second temperature below the firsttemperature. In some embodiments, the region 77 of skin of secondtemperature can remain substantially undamaged. In some embodiments, theregion 77 of skin of second temperature can form a second sub-zone 78 ofthermal injury.

FIG. 7C shows yet another exemplary treatment of skin using cooling,specifically a skin surface 69 with at least one first 79 region and atleast one second 89 region. The at least one first 79 region and atleast one second 89 region can form a regular or irregular array. In onetreatment, the target region can be cooled to produce at least one first79 region at a first temperature and at least one second 89 region at asecond temperature, the first temperature being greater than the secondtemperature. The at least one first 79 region can correspond to the atleast one first sub-zone, and the at least one second 89 regioncorresponding to the at least one second sub-zone. In another example,the method can include cooling the target region of skin to produce atleast one first 79 region cooled to a first depth and at least onesecond 89 region cooled to a second depth, the first depth being lessthan the second depth. The at least one first 79 region can correspondto the at least one first sub-zone, and the at least one second 89region corresponding to the at least one second sub-zone. In general,the depth and/or temperature within the target region can be controlledby the duration and/or temperature of the cooling. For example, agreater duration can cool to a greater depth and a lower temperature cancool to a lower temperature.

Sub-zones of thermal damage can form different geometries. In variousembodiments, sub-zone geometries can include cylinders, cones, cuboids,spheroids, ellipsoids, and ovoids. Any of these sub-zone geometries canbe overlaid with, or combined with, a substantially continuous surfacethermal injury.

FIG. 8A shows an exemplary embodiment of a surface 80 of a treatedregion of skin with a pattern of varying depths of thermal injury. Aregular two-dimensional array of a plurality of sub-zones of a firstdepth 82 of thermal injury are adjacent to a plurality of sub-zone of asecond depth 84 of thermal injury.

In another embodiment, a plurality of sub-zones of a first depth ofthermal injury adjacent to a plurality of sub-zones of a second depth ofthermal injury can form a one-dimensional array (e.g., a curvilinearpattern). Such a pattern can, for example, trace the contour of awrinkle, vein, scar, or skin defect. In certain embodiments, methods caninclude varying a pattern over different parts of the skin to achievedifferent desired effects (e.g., to produce a pattern of surface injuryin an area with surface wrinkles, while producing a pattern ofsub-surface injury in an area for skin tightening with less surfaceinjury).

FIG. 8B shows an exemplary embodiment of a surface 86 of a treatedregion of skin with a pattern of varying depths of thermal injury. Anirregular array of a plurality of sub-zones of a first depth 87 ofthermal injury are adjacent to a plurality of sub-zone of a second depth88 of thermal injury.

FIG. 9 shows a ray trace 90 of modulated electromagnetic radiation. Theelectromagnetic radiation is represented by a plurality of rays 91,which are emitted from a fiber face 93. The rays 91 are imaged by twolenses 95 and then spatially modulated by a micro lens 97 array beforedelivery to the skin 99 surface. A first region 92 of the skin surface,upon which more rays 91 are incident, can correspond to a first sub-zoneof a first depth of thermal injury. A second region 94 of the skinsurface, upon which fewer rays 91 are incident, can correspond to asecond sub-zone of a second depth of thermal injury.

FIG. 10 shows a contour plot 100 of energy density on skin created bymodulated electromagnetic radiation. A position of high 101 energydensity can correspond to a first sub-zone of a first depth of thermalinjury and a position of low 102 energy density can correspond to asecond sub-zone of a second depth of thermal injury. The legend 103 ofthe contour plot 100 shows the energy density in units of W/mm². Thecontour plot 100 represents an area of about 7 mm by about 7 mm.

FIG. 11 shows a plot 110 of intensity variation across skin created bymodulated electromagnetic radiation. The y-axis shows the intensity ofenergy in arbitrary units (a.u.) and the x-axis shows the position inmicrons. A position of high 111 energy density can correspond to a firstsub-zone of a first depth of thermal injury and a position of low 112energy density can correspond to a second sub-zone of a second depth ofthermal injury.

While the invention has been particularly shown and described withreference to specific embodiments, it should be understood by thoseskilled in the art that various changes in form and detail may be madetherein without departing from the spirit and scope of the invention asdefined by the appended claims.

1. A method for treating skin, the method comprising delivering a beamof radiation to a target region of the skin to cause a zone of thermalinjury including a lateral pattern of varying depths of thermal injurydistributed along the target region, the lateral pattern including atleast one first sub-zone of a first depth of thermal injury laterallyadjacent to at least one second sub-zone of a second depth of thermalinjury, wherein (i) the first depth is greater than the second depth,(ii) the at least one first sub-zone of the first depth and the at leastone second sub-zone of the second depth extend from a surface of thetarget region of the skin to form a substantially continuous surfacethermal injury, and (iii) the at least one first sub-zone of the firstdepth and the at least one second sub-zone of the second depth aresubstantially heated to at least a critical temperature to cause thethermal injury.
 2. The method of claim 1 wherein the lateral pattern hasa substantially sinusoidal cross sectional injury profile.
 3. The methodof claim 1 further comprising delivering the beam of radiation to thetarget region to form a one-dimensional lateral pattern of varyingdepths of thermal injury.
 4. The method of claim 1 further comprisingdelivering the beam of radiation to the target region to form atwo-dimensional lateral pattern of varying depths of thermal injury. 5.The method of claim 1 wherein at least one of the first depth and thesecond depth are between about 2 mm and about 0.02 mm.
 6. The method ofclaim 1 further comprising heating the at least one first sub-zone andthe at least one second sub-zone to substantially the same temperature.7. The method of claim 1 wherein the first depth is about 1.5 mm and thesecond depth is about 0.05 mm.
 8. The method of claim 1 wherein thecritical temperature is below about 100° C., 95° C., 90° C., 85° C., 80°C., 75° C., 70° C., 65° C., 60° C., 55° C., or 50° C.
 9. The method ofclaim 1 wherein the thermal injury includes at least one of ablation,coagulation, necrosis, and acute thermal injury of skin.
 10. The methodof claim 1 further comprising cooling the surface of the skin, tocontrol the surface thermal injury.
 11. The method of claim 1 furthercomprising cooling the surface of the skin, to prevent unwanted surfacethermal injury.
 12. The method of claim 1 further comprising deliveringa beam of radiation having a first wavelength to the at least one firstsub-zone to cause the first depth of thermal injury and a beam ofradiation having a second wavelength to the at least one second sub-zoneto cause the second depth of thermal injury.
 13. The method of claim 1further comprising delivering a beam of radiation having a first fluenceto the at least one first sub-zone to cause the first depth of thermalinjury and a beam of radiation having a second fluence to the at leastone second sub-zone to cause the second depth of thermal injury.
 14. Themethod of claim 1 further comprising delivering a beam of radiationhaving a first pulse duration to the at least one first sub-zone tocause the first depth of thermal injury and a beam of radiation having apulse duration to the at least one second sub-zone to cause the seconddepth of thermal injury.
 15. The method of claim 1 further comprising atleast two first sub zones of the first depth are separated by a centerto center distance of about 0.05 mm to about 20 mm.
 16. The method ofclaim 1 wherein the at least one first sub-zone of the first depth hasan aspect ratio of diameter:depth up to about 0.1:10.
 17. The method ofclaim 1 wherein the at least one second sub-zone of the second depth hasan aspect ratio of diameter:depth up to about 0.1:10.
 18. The method ofclaim 1 further comprising cooling the target region of skin to produceat least one first region at a first temperature and at least one secondregion at a second temperature, the first temperature being greater thanthe second temperature, the at least one first region corresponding tothe at least one first sub-zone, and the at least one second regioncorresponding to the at least one second sub-zone.
 19. The method ofclaim 1 further comprising cooling the target region of skin to produceat least one first region cooled to a first depth and at least onesecond region cooled to a second depth, the first depth being less thanthe second depth, the at least one first region corresponding to the atleast one first sub-zone, and the at least one second regioncorresponding to the at least one second sub-zone.
 20. A method fortreating skin, the method comprising: delivering a beam of radiation toa first portion of a target region of the skin to heat the first portionto at least a critical temperature to cause a first thermal injury;translating the beam of radiation to a second portion of the targetregion; delivering the beam of radiation to the second portion of thetarget region to heat the second portion to at least the criticaltemperature to cause a second thermal injury, the first thermal injuryand the second thermal injury extending from a surface of the targetregion of the skin to form a substantially continuous surface thermalinjury and forming a lateral pattern of varying depths of thermal injurydistributed along the target region.
 21. The method of claim 20 furthercomprising varying at least one of a fluence, intensity, wavelength, andrate of translation of the beam of radiation to control the depth of thefirst thermal injury and the second thermal injury.
 22. An apparatus fortreating skin comprising: a source of a beam of radiation; a modulatorreceiving the beam of radiation and forming a modulated spatial profileof the beam including a first plurality of first regions at a firstfluence and a second plurality of second regions at a second fluence,the first fluence being greater than the second fluence, each firstregion being spaced from an adjacent first region by a respective secondregion; and a device for delivering the beam of radiation to a targetregion of skin to cause a zone of thermal injury including a lateralpattern of varying depths of thermal injury distributed along the targetregion, the lateral pattern including at least one first sub-zone of afirst depth of thermal injury laterally adjacent to at least one secondsub-zone of a second depth of thermal injury, wherein (i) the firstdepth is greater than the second depth, (ii) the at least one firstsub-zone of the first depth and the at least one second sub-zone of thesecond depth extend from a surface of the target region of the skin toform a substantially continuous surface thermal injury, and (iii) the atleast one first sub-zone of the first depth and the at least one secondsub-zone of the second depth are substantially heated to at least acritical temperature to cause the thermal injury.
 23. The apparatus ofclaim 22 further comprising a cooling system for controllably cooling atleast a portion of the target region of skin, to control the thermalinjury within the target region.
 24. The apparatus of claim 22 furthercomprising a cooling system for cooling the target region of skin toproduce at least one first region at a first temperature and at leastone second region at a second temperature, the first temperature beinggreater than the second temperature, the at least one first regioncorresponding to the at least one first sub-zone, and the at least onesecond region corresponding to the at least one second sub-zone.
 25. Theapparatus of claim 22 further comprising a cooling system for coolingthe target region of skin to produce at least one first region cooled toa first depth and at least one second region cooled to a second depth,the first depth being less than the second depth, the at least one firstregion corresponding to the at least one first sub-zone, and the atleast one second region corresponding to the at least one secondsub-zone.